Phospholipase C beta 4 in mouse hepatocytes: rhythmic expression and cellular distribution

Circadian regulated physiological processes have been well documented in the mammalian liver. Phospholipases are important mediators of both cytoplasmic and nuclear signaling mechanisms in hepatocytes, and despite a potentially critical role for these enzymes in regulating the temporal aspect of hepatic physiology, their involvement in the circadian liver clock has not been the subject of much investigation. The phospholipase C beta4 (PLCbeta4) enzyme is of particular interest as it has been linked to circadian clock function. In general, there is no knowledge of the role of the PLCbeta4 isozyme in mammalian hepatocytes as this is the first report of its expression in the mammalian liver.

We found that in the liver of mice housed on a light:dark cycle, PLCbeta4 protein underwent a significant circadian rhythm with a peak occurring during the early night. In constant darkness, the protein rhythm was more robust and peaked around dusk. We also observed a significant oscillation in plcbeta4 gene expression in the livers of mice housed in both photoperiodic and constant dark conditions. The cellular distribution of the protein in hepatocytes varied over the course of the circadian day with PLCbeta4 primarily cytoplasmic around dusk and nuclear at dawn.

Our results indicate that PLCbeta4 gene and protein expression is regulated by a circadian clock in the mouse liver and is not dependent on the external photoperiod. A light-independent daily translocation of PLCbeta4 implies that it may play a key role in nuclear signaling in hepatocytes and serve as a daily temporal cue for physiological processes in the liver.